1. Field of the Invention
The anxiolytic activity of benzodiazepines is well known. The presence of brain specific benzodiazepine receptors in membranes from the rat brain is also well established (cf. Squires, R. F. et al., Nature 266 (1977), page 732).
Highly significant correlations between the affinities of various benzodiazepines for the benzodiazepine receptor site in the rat brain on the one hand and clinically predictive pharmacological activities in mammals on the other hand, strongly suggest that the benzodiazepine receptor in vitro is related to a physiologically relevant receptor for benzodiazepines in vivo.
2. Description of the Prior Art
Until now the binding site for benzodiazepine (.sup.3 H-diazepam) in the rat brain has been considered as highly specific for benzodiazepines, since none of the non-benzodiazepine substances demonstrated significant efficacy as .sup.3 H-diazepam displacers. This efficacy is measured by K.sub.i values in micro moles calculated by using the equation: EQU K.sub.i =IC.sub.50 [(1+C)K.sub.D ]
wherein:
C=the concentration of .sup.3 H-diazepam,
K.sub.D =the affinity constant=2,74 .mu.M, and
IC.sub.50 =the concentration causing 50% inhibition of .sup.3 H-diazepam binding.
Non-benzodiazepines were considered up to now as having no significant affinity for .sup.3 H-diazepam binding site, since their K.sub.i is higher than 100 .mu.M. For example, Braestrup and Squires in the European Journal of Pharmacology, 48 (1978) 263-270 at page 268 disclose that they did not fine any compounds other than benzodiazepines with significant affinity for the .sup.3 H-diazepam binding site (K.sub.i &gt;0.1 mM).